Percutaneous administration preparations

ABSTRACT

Provided is a composition for percutaneous administration containing a mixture of polymers forming a surface-segregated film, and (B) an active ingredient. The composition provides excellent percutaneous absorption efficacy of the active ingredient, particularly, a water-soluble active ingredient, has excellent feeling and is convenient to use.

TECHNICAL FIELD

[0001] The present invention relates to a composition for percutaneousadministration which is particularly useful for percutaneousadministration of a water soluble active ingredient and is excellent infeeling upon use and convenient to use.

BACKGROUND ART

[0002] Known methods for administration of pharmacological activeingredients are percutaneous administration, oral administration,injection, and the like. In particular, percutaneous administration iscommonly used to decrease degradation in digestive tracts or first passeffect compared with oral administration, to reduce pain or burden givento patients compared with injection, and to continue administration forlong hours. However, the skin essentially serves as a barrier forpreventing invasion of foreign substances from the outside orevaporation of moisture in the body. The permeability of skin is lowerthan that of the general biomembrane.

[0003] A cataplasm using a hydrous gel preparation is one example of ameans permitting efficient percutaneous absorption of pharmacologicalactive ingredients. Accelerating efficacy of percutaneous absorption ofthe cataplasm is based on hydration and expansion of most outer layer ofthe epidermis, which is the horny cell layer of the skin and serves as abarrier of percutaneous absorption.

[0004] Since a cataplasm is formed by applying a hydrous gel containingan active ingredient to a backing material such as nonwoven cloth, ithas suitable thickness and therefore lacks flexibility. In addition,adhesion of the hydrous gel layer to the skin is insufficient. As aresult, it causes uncomfortable feeling during use, easily peels offfrom the skin by failing to move, and fails to provide sufficientacceleration of percutaneous absorption.

[0005] A composition for percutaneous administration containing asubstance softening or hydrating the keratin layer such as urea orpolyol has been proposed. However, efficacy of percutaneous absorptionof active ingredients is still insufficient.

[0006] An object of the present invention is therefore to provide acomposition for percutaneous administration which exerts an excellentpercutaneous absorption performance of an active ingredient, hasexcellent feeling and is convenient to use.

DISCOLSURE OF HE INVENTION

[0007] The inventors have found that a composition for percutaneousadministration comprising a polymer mixture which forms asurface-segregated film and an active ingredient provides efficientpercutaneous absorption of an active ingredient when applied to theskin, has excellent feeling and is convenient to use.

[0008] The present invention therefore provides a composition forpercutaneous administration comprising the following components (A) and(B):

[0009] (A) a polymer mixture which forms a surface-segregated film; and

[0010] (B) an active ingredient.

BRIEF DESCRIPTION OF THE DRAWING

[0011]FIG. 1 illustrates the amount of a composition for percutaneousabsorption of VC-PMG.

BEST MODE FOR CARRYING OUT THE INVENTION

[0012] In the present invention, the term “surface-segregated film”means a film whose component has been partially segregated in thevicinity of the film surface. This surface segregation phenomenon can beobserved by a surface analyzer such as FT-IR-ATR (Fourier TransformInfrared Spectrophotometer-Attenuated Total Reflection), XPS (X-rayPhotoelectron Spectroscopy), or EDX (Energy Dispersion X-ray analysis)or an electron microscope such as TEM (Transmission ElectronMicroscope).

[0013] In the present invention, such surface segregation is caused by acomposition comprising a mixture of at least two polymers havingdifferent properties. A film formed from a composition containing atleast two polymers having different surface tension has a segregatedsurface, because owing to lowering in the surface energy of the film, apolymer component having lower surface tension γ is segregatedpreferentially on the surface.

[0014] Preferably, such a polymer mixture has Δγ of 3 mN/m or greater,especially 5 to 60 mN/m, which is a difference of the surface tensionbetween two of these polymers, the maximum surface tension γ₂ andminimum surface tension γ₁.

[0015] First, contact angles (20°) of water and ethylene glycol on thefilm surface of the polymer prepared in a manner known per se in the artare measured, then surface tension is determined in accordance with themethod of Hata, etc. (Journal of the Adhesion Society of Japan, 8(3),9(1972)). When liquid (L) is contacted with the surface of polymer film(S) at a contact angle of θ the following equation can be establishedbetween surface tension and interfacial tension.

γ_(S)−γ_(SL)=γ_(L) cos θ  (1)

γ_(SL)=γ_(L)+γ_(S)−2{square root}{square root over (γ_(S) ^(d)×γ_(L)^(d))}−2{square root}{square root over (γ_(S) ^(p)×γ_(L) ^(p))}  (2)

γ_(S)=γ_(S) ^(d)+γ_(S) ^(p)  (3)

γ_(L)=γ_(L) ^(d)+γ_(L) ^(p)  (4)

[0016] (wherein, γ_(s) represents surface tension of the polymer film,γ_(SL) represents the interfacial tension between the polymer film andliquid, γ_(L) represents the surface tension of the liquid, γ_(S) ^(d),γ_(L) ^(d) represent non-polar sections of the surface tension of thepolymer film and liquid, respectively, and γ_(S) ^(p), γ_(L) ^(p)represent polar sections of the surface tension of the polymer film andliquid, respectively).

[0017] Here, the equations (1) and (2) lead to the following equation(5):

γ_(L)+γ_(L) COS θ=2{square root}{square root over (γ_(S) ^(d)×γ_(L)^(d))}+2{square root}{square root over (γ_(S) ^(P)×γ_(L) ^(P))}  (5)

[0018] The surface tension at 20° C. is as follows: in the case ofwater, γ_(L)=72.0 mN/m, γ_(L) ^(d)=23.2 mN/m and γ_(L) ^(p)=48.8 mN/m,while in the case of ethylene glycol, γ_(L)=48.9 mN/m, γ_(L) ^(d)=33.4mN/m and γ_(L) ^(p)=15.5 mN/m. These values and the data of contactangle are substituted for the above equation (5) to determine γ_(s) ^(d)and γ_(s) ^(p), whereby γ_(s) is available from the equation (3).

[0019] The component (A) includes a mixture of polymers forming asurface-segregated film. The advantage of the present invention isexhibited fully by selecting two polymers, for example, which havedifferent surface tension so that the Δγ will be 3 mN/m or greater,especially 5 to 60 mN/m. Such polymers are selected widely from thecombination of a hydrophobic polymer and a hydrophilic polymer.Preferred combination of a hydrophobic polymer and a hydrophilic polymeris described below. The weight ratio of a hydrophobic polymer to ahydrophilic polymer preferably ranges from 5:95 to 95:5, especially15:85 to 85:15 with regard to surface segregation.

[0020] As a hydrophobic polymer, those having a surface tension of 10 to45 mN/m, especially 10 to 40 mN/m are preferred. Examples includefilm-forming silicone polymers and polymers having a fluorinated carbonchain. In addition, those taking a solid form at normal temperature andnormal pressure but being soluble or dispersible in a volatile solventare preferred for facilitating formulation.

[0021] Examples of the silicone polymer include oxazoline-modifiedorganopolysiloxanes, vinyl copolymers containing a polysiloxanemacromer, organopolysiloxanes having a sugar residue, alkyl-modifiedorganopolysiloxanes and high polymerization organopolysiloxanes (asdescribed, for example, in Japanese Patent Application Laid-Open No.09-291020, Japanese Patent Application Laid-Open No. 06-145023, JapaneseLanguage Laid-Open Publication No. 09-501728 (=WO95/06078), and“Fragrance Journal, 21(12), 56(1993)”, Ibid, 24(12), 21-26(1996)).)

[0022] Preferred oxazoline-modified organopolysiloxanes areorganopolysioloxanes (Japanese Patent Application Laid-Open No.09-291020) comprising an organopolysiloxane segment (a) and a segmentderived from open-ring polymerization of an oxazoline monomer, that is,a poly(N-acylalkyleneimine) segment which is bonded to the segment (a)at the end or side chain in the molecule thereof via ahetero-atom-containing alkylene group and consists of repeating unitsrepresented by the following formula (1):

[0023] (wherein, R¹ represents a hydrogen atom, a C₁₋₂₂ alkyl group, acycloalkyl group, an aralkyl group or an aryl group, and k stands for 2or 3), wherein the weight average molecular weight ranges from 50,000 to500,000 and a weight ratio of (a) to (b) ranges from 98:2 to 40:60. Thepolystyrene equivalent weight average molecular weight is determined bygel permeation liquid chromatography (GPC) using chloroform as adeveloping solvent.

[0024] Examples of the polymer having a fluorinated carbon chain includehomopolymers of a fluorine-containing vinyl monomer, copolymerscontaining a fluorine-containing vinyl monomer as a constituent(Japanese Patent Application Laid-Open No. 11-100306) and vinylidenefluoride-hexafluoroacetone copolymer.

[0025] Examples of the fluorine-containing vinyl monomer includefluoroalkyl (meth)acrylates, fluoroalkyl (meth)acrylic amide esters,fluoroalkyl vinyl ethers and fluoro-α-olefins, of which (meth)acrylateshaving a fluoroalkyl group (having 6 to 12 carbon atoms) are preferred.As the fluoroalkyl group, polyfluoroalkyl and perfluoroalkyl groups canbe exemplified.

[0026] As the monomer copolymerizable with the fluorine-containing vinylmonomer, preferred are alkyl (meth)acrylates having a linear or branchedalkyl group having at least 8 carbon atoms and/or dimethylpolysiloxanecompounds having, at one end of the molecular chain, a radicalpolymerizable group. Fumarate esters can also be given as anotherexample.

[0027] As the hydrophobic polymer, two or more hydrophobic polymers maybe mixed. The composition contains the hydrophobic polymer in an amountof 0.001 to 30 wt. % (which will hereinafter be called “%”, simply),preferably 0.005 to 20%, more preferably 0.01 to 10%. Oxazoline-modifiedorganopolysiloxanes are particularly preferred.

[0028] As the hydrophilic polymer, its surface tension ranging from 30to 70 mN/m, especially 40 to 70 mN/m is preferred. Examples includenatural or synthetic film-forming polymers, more specifically,polysaccharides such as acidic heteropolysaccharides,mucopolysaccharides and cellulose derivatives, polypeptides,hydroxyl-containing polymers such as polyvinyl alcohol and polyethyleneglycol, and water-soluble polymers such as cationic-group-containingpolymers.

[0029] More specific examples include acidic heteropolysaccharidesderived from the callus of plants belonging to Polianthes L., hyaluronicacid, arabic gum, guar gum, xanthan gum, pectin, locust bean gum,carrageenan, maltotriose, collagen and derivatives thereof, pullulan,chitin and derivatives thereof, chitosan and derivatives thereof,cationated cellulose, carboxymethyl cellulose, methyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,hydroxypropylmethyl cellulose, polyvinyl alcohol, polyethylene glycoland poly(methacryloyloxyethyltrimethylammonium chloride) (as described,for example, in Fragrance Journal, 21(12), 13-73(1993)).

[0030] Among the hydrophilic polymers, water-soluble polymers having apolystyrene equivalent weight average molecular weight of 4000 to 500000as measured by GPC, especially 10000 to 500000 are preferred. Morespecifically, polyvinyl alcohol, polyethylene glycol, collagen andderivatives thereof, pullulan, chitin and derivatives thereof, andchitosan and derivatives thereof are preferred, with polyvinyl alcoholbeing especially preferred.

[0031] Two or more hydrophilic polymers may be mixed. The compositioncontains the hydrophilic polymers in an amount of 0.001 to 30%,especially 0.005 to 20%, more preferably 0.01 to 10%.

[0032] As the combination of polymers forming a surface-segregated film,that of a silicone polymer or a polymer having a fluorinated carbonchain and a water soluble polymer, especially that of anoxazoline-modified organopolysiloxane and polyvinyl alcohol ispreferred.

[0033] Although no particular limitation is imposed on the component (B)insofar as it is a substance exhibiting effects such as corium firming,whitening, blood-circulation stimulating, lipolysis accelerating oranti-inflammatory effects, water-soluble substances are desired from theviewpoint of percutaneous absorption. A substance having markedly smallsolubility in water may be employed. Specific examples include plantextracts, animal extracts, guanidine derivatives, catecholamines, aminoacids, vitamins, hormones and organic acids.

[0034] Examples of the plant extracts include those having coriumfirming effects Ginkgo biloba (gingko), Foeniculi Fructus (fennel),kiwi, Morus bombycis (mulberry), Gentiana lutea (gentian), red algae,Arctium lappa (burdock), Salvia officinalis (sage), Lentinus edodes(shiitake mushroom), Perilla frutescens (perilla), FilipendulaMultijuga, Fucus vesiculosis (bladderwrack, sea weed), peach kernel,Panax ginseng (carrot), Allium sativum (garlic), Poria cocos (poria),Humulus lupulus (hops), Mutan Cortex (Moutan Bark), Pimpinella major,Lactuca sative (lettuce), Astragalus membranaceous (astragalus) andRosmarinus officinalis (rosemary); those having whitening effects suchas Prunus amygdalus (almond), Althea officinale (althea), aloe, RosaeFructus (rose fruit, or Rosa multiflora), Scuttelaria baicalensis (Huangqin), Puerariae Radix (Pueraria Root, or Pueraria lobata), ChamomillaeFlos (German chamomile), Gardenia jasminoides (zhii zi, GardeniaeFructus), Sophora flavescens Aiton (Sophorae Radix), chlorella, ricebran, Paeoniae lactiflora (white peony), ziyu (Sanguisorba officinalis,burnet), Morus alba (sang bai pi, mulberry), Glycine max (soybean),Camellia sinensis (tea), Carthami Flos (safflower), Aesculushippocastanum (horse chestnut), Melissa officinalis (lemon balm) andCoicis Semen (Coix lacryma-jobi var. ma-yuen); those having bloodcirculation accelerating effects such as Angelica keisukei, Arnicamontana (arnica), Foeniculum officinale (fennel), Isodon japonicus Hara(Isodonis Herba), Daucus Carota (carrot), Oryza sativa (rice), Crataeguscuneata (Japanese howthorn), Acorus calamus (sweet flag), Crataegusoxycantha (howthorn), Juniperus communis, Ligusticum wallichii (Chineselovage), Swertiae Herba (Swertia Herb), Thymus vulgaris (garden thyme),Citrus reticulata (Citrus unshiu), Capsicum tincture, Angelicae sinensis(angelica), Aurantii Pericarpium (bitter orange peel), Ruscus aculeatus(butcher's bloom), Vitis vinifera (grape), Tilia japonica (lime), Citrusjunos and Rosa canina (rose hip); those having lipolysis acceleratingeffects, for example, thistles such as Cephalonoplos segetnum (Bieb.)Kitam. and Cirsium japonicum DC (Japanese Patent Application Laid-OpenNo. 08-301780 (=U.S. Pat. No. 5,698,199)), caffeine, Cinnamomi Cortex(cinnamon bark) and Eriobotrya japonica Lindl. (loquat); those havinganti-inflammatory effects Gambir, Echinacea, Phellodendri Cortex (amurcork tree or Phellodendron amurense), Hypericum perforatum (St. John'swort), Citrus sinensis (orange), Valeriana fauriei Briquet, Artemisiacapillaris Thunb., Cucumis sativus (cucumber), Geranii Herba (GeraniumHerb), Lithospermum erythrorhizon Sieb. et Zucc., Hedera helix, Achilleamillefolium (yarrow), Ziziphus jujuba (Chinese dates), Calendulaofficinalis (pot marigold), Houttuynia cordata (Houttuyniae Herba,Houttuynia Herba), Potentilla erecta, Petroselinum crispum (parsley),Parietaria officinalis, Santalum album (sandalwood), Prunus persica(peach), Centaurea cyanus (cornflower), Eucalyptus globulus (eucalyptus)and Lavandula angustifolia (lavender); those having hair-growthaccelerating effects such as Persea americana (avocado), Aloe vera(aloe), Nasturtium officinalis (watercress), Symphytum officinale(comfrey), Asarum sieboldii (wild ginger), Xanthoxyum piperitum (Japanpepper), Rehmannia glutinosa (di huang), Mentha piperita (peppermint),Syzygium aromaticum (clove), Tussilago farfara (coltsfoot) andHaematoxylum campechianum (logwood); and those having anti-aging effectssuch as Oolong tea, Cinchona succirubra (peruvian bark), Betulaverrucosa (birch) and Glechoma hederacea (ground ivy); while examples ofthe animal extracts include placenta extract having whitening effects,milk and royal jelly having blood circulation accelerating effects,honey having anti-inflammatory effects and pearl protein having cellactivating action (for example, as described in Fragrance Journal 23(8),41 to 47(1995), Ibid 24(8), 62 to 67(1996)).

[0035] As the component (b), those exemplified above may be used eithersingly or in combination. It is preferably added to a composition in anamount of 0.00001 to 30%, especially 0.0001 to 20%. When the activeingredient is a plant or animal extract, the amount does not include theextracting solvent but its solid content. As the extract, commerciallyavailable ones in the liquid form may be used as is.

[0036] The composition for percutaneous administration of the presentinvention can be prepared by adding the active ingredient in a solutionor dispersion obtained by dissolving or dispersing at least two polymersforming a surface-segragated film to a volatile solvent.

[0037] As the volatile solvent, those having a boiling point of 210° C.or less, preferably 40 to 110° C. are preferred. Water and loweralcohols (having 1 to 3 carbon atoms) are more preferred, with water andethanol being especially preferred. The volatile solvent is preferablyadded to the composition in an amount of 30 to 98%, especially 50 to95%.

[0038] When the composition for percutaneous administration of thepresent invention is applied to the skin, a film is formed with thepolymer having lower surface tension being surface-segregated on the airinterface side.

[0039] The composition for percutaneous administration of the presentinvention is prepared in a conventional manner by adding variousoptional components ordinarily employed for cosmetics, quasi-drugs ordrugs within an extent not impairing the advantage of the presentinvention.

[0040] No particular limitation is imposed on the various optionalcomponents usable here, but examples include oleaginous agents, morespecifically, hydrocarbons, ester oils, higher fatty acids, higheralcohols, naturally extracted sphingosine derivatives and syntheticceramide analogs (Japanese Patent Application Laid-Open No. 62-228048(=EP-A-227994), Japanese Patent Application Laid-Open No. 08-319263(=U.S. Pat. No. 5,863,945)), polyhydric alcohols, thickeners, fattyacids, surfactants, powders, clay minerals, inorganic salts, pHregulators, chelating agents, antioxidants, antiseptics, colorants,ultraviolet absorbers and perfumes.

[0041] Although the composition for percutaneous administration of thepresent invention can be prepared in various forms such as solution,paste, gel, emulsion and dispersion, the solution, paste and gel inwhich the active ingredient has been dissolved are preferred forpercutaneous absorption. The composition for percutaneous administrationof the present invention is preferred to have a viscosity of 0.01 to 200Pa·s (25° C.), preferably 0.1 to 100 Pa·s from the viewpoint ofconvenient use.

EXAMPLE Example 1

[0042] A composition for percutaneous administration (invention product)was obtained in a gel form by stirring and mixing the component (2)having the composition as shown in Table 1 at 80° C., cooling theresulting solution to room temperature, and mixing it with the component(1) mixed at room temperature in advance. As a comparative product, thecomposition as shown in Table 1 was applied to a nonwoven cloth, wherebya cataplasm was prepared. Its viscosity as measured at 25° C. by a B8Lviscometer (manufactured by Tokimec, Inc.) under the conditions of a No.3 rotor, 12 rpm and 60 seconds was 5.0 Pa·s. TABLE 1 % InventionComparative Component product product Component (1): Oxazoline-modifiedorganopolysiloxane 3.78 0 (30% ethanol solution) ¹⁾ Ethanol 5 0 Succinicacid 0.1 0 Magnesium ascorbyl L-phosphate 0.05 0.05 Disodium edatate 0.20.2 l-Menthol 0.1 0 Component (2): Polyvinyl alcohol ²⁾ 0.48 0Hydroxyethyl cellulose 1 0 Propylene glycol 8 0 Methyl paraoxybenzoate0.2 0.2 Purified water Balance Balance Polyacrylic acid 0 1.5 Sodiumpolyacrylate 0 5.5 Dried aluminum hydroxide gel 0 0.2 Silicic anhydride0 2 Glycerin 0 35

[0043] (1) Test Method on Percutaneous Absorption:

[0044] Magnesium ascorbyl L-phosphate (VC-PMG) employed as awater-soluble active ingredient was added to each composition as shownin Table 1.

[0045] The abdominal skin of male Wistar rats 9 to 10 weeks of ageshaven in advance was enucleated together with their subcutaneous tissueand was divided by a median line. The skin piece was mounted on animproved Franz diffusion cell (inner diameter: 2.5 cm; skin area: 4.9cm²). After physiological saline was filled in a receptor tank, stirringwas conducted continuously by a stirrer. The surface of the skin wastreated in a warm-water bath (water of 38° C. for 10 minutes) and then,a predetermined amount (40 mg) of the preparation was applied to theskin surface. It was allowed to stand under the circumstance of 30° C.and 65% RH. At regular intervals, 50 μL portions were sampled from thereceptor tank. The VC-PMG in physiological saline which had permeatedthrough the skin was analyzed and its amount was determined by HPLC. Theresults are shown in FIG. 1.

[0046] The determination of the amount of VC-PMG by HPLC was conductedby ion column chromatography using a reversed phase column under thefollowing conditions:

[0047] HPLC column: Lichrosorb RP-18 4.5Ø×150 mm/5 μm

[0048] Eluent:

[0049] 0.08M acetic acid/sodium acetate

[0050] 2.8 mM Tetra-n-butylammonium hydrogensulfate

[0051] 0.1 mM EDTA-2Na

[0052] 2% MeOH aq

[0053] Flow rate: 0.8 mL/min

[0054] Temperature: 30° C.

[0055] Detection: 260 nm

[0056] As apparent from FIG. 1, the invention product was excellent inpercutaneous absorption of VC-PMG.

[0057] (2) Evaluation of Feeling Upon Use and Convenience:

[0058] Feeling upon use and convenience of each preparation wereevaluated by a panel of 20 female experts who applied it to theirabdomen (applied region: 10 cm×10 cm). The feeling upon use was rankedas 5 points when it was good, 4 points when slightly good, 3 points whenneither good nor bad, 2 points when not so favorable and 1 point whennot favorable, while the convenience was ranked as 5 points when thepreparation was judged convenient, 4 points when judged slightlyconvenient, 3 points when judged neither convenient nor inconvenient, 2points when judged not so convenient and 1 point when judgedinconvenient. Evaluation was expressed by the average of 20 experts. Theresults are shown in Table 2. TABLE 2 Item to be Invention Comparativeevaluated product product Feeling upon use 4.5 3.0 Convenience 5.0 2.0

[0059] As is apparent from Table 2, the invention product was superiorto the cataplasm of Comparative product in both feeling upon use andconvenience. EXAMPLE 2 (Component) (%) Oxazoline-modifiedorganopolysiloxane 3.0 (30% ethanol solution) ³⁾ Polyvinyl alcohol ⁴⁾1.0 Propylene glycol 5.0 Hydroxyethyl cellulose 0.72-(2-Hydroxyethoxy)ethylguanidine succinate 2.5 Extract of Sanguisorbaoifficinalis (ziyu) 1.0 Extract of Fucus vesiculosis (bladderwrack) 1.0Ethanol 5.0 Purified water Balance

[0060] Viscosity: 1.5 Pa·s (Component) (%) Oxazoline-modifiedorganopolysiloxane 3.5 (30% ethanol solution) Polyvinyl alcohol 0.5Succinic acid 0.1 1-(2-hydroxyethylamino)-3-isostearyl oxy-2-propanol0.2 Glycerin 4.0 Guar gum 0.8 Extract of Eucalyptus globulus(eucalyptus) 1.5 Extract of Tilia japonica (lime) 1.0 Disodium edatate0.2 Methylparaben 0.2 Ethanol 10.0 Purified water Balance Viscosity:2.16 Pa · s

Example 3

[0061] (Component) (%) Oxazoline-modified organopolysiloxane 3.5 (30%ethanol solution) Polyvinyl alcohol 0.5 Succinic acid 0.1 Propyleneglycol 5.0 Xanthan gum 0.8 Extract of Chamomillae Flos (Germanchamomile) 0.5 Extract of Thistle 1.0 Extract of Fucus vesiculosis(bladderwrack) 1.0 Caffeine 0.2 Disodium edatate 0.2 Methylparaben 0.2Ethanol 10.0 Purified water Balance Viscosity: 3.35 Pa · s

[0062] EXAMPLE 5 (Component) (%) Oxazoline-modified organopolysiloxane3.5 (30% ethanol solution) Pollulan ⁵⁾ 1.0 Propylene glycol 4.0Hydroxyethylcellulose hydroxypropyl cellulose stearyl ether 0.8 sodiumhydroxypropylsulfonate Extract of Althea Officinalis (althea) 0.8Ascorbic acid 1.0 Methylparaben 0.2 Ethanol 10.0 Purified water Balance

[0063] Viscosity: 17.1 Pa·s EXAMPLE 6 (Component) (%) Oxazoline-modifiedorganopolysiloxane 3.5 (30% ethanol solution) Polyethylene glycol ⁶⁾ 0.5Glycerin 4.0 Synthetic ceramide analog ⁷⁾ 0.1 Phytosphingosine ⁸⁾ 0.2Polyoxyethylene sorbitan monostearate (20 E.O.) 0.7 Sorbitanmonostearate 0.3 Cholesterol 0.3 Xanthan gum 0.8 Extract of Sanguisorbaofficinalis (ziyu) 1.0 Disodium edatate 0.2 Methylparaben 0.2 Ethanol10.0 Purified water Balance

[0064] Viscosity: 1.9 Pa·s

[0065] Compositions for percutaneous administration obtained in Examples2 to 6 can be applied to any desired part of the body, are useful forpercutaneous administration of a water soluble active ingredient, haveexcellent feeling and are convenient to use.

INDUSTRIAL APPLICABILITY

[0066] The composition for percutaneous administration of the presentinvention is excellent in percutaneous absorption of an activeingredient, particularly, a water-soluble active ingredient, hasexcellent feeling and is convenient to use.

1. A composition for percutaneous administration comprising thefollowing components (A) and (B): (A) a mixture of polymers which formsa surface-segregated film; and (B) an active ingredient.
 2. Acomposition according to claim 1, wherein the component (A) is a mixtureof at least two polymers having different surface tension.
 3. Acomposition according to claim 1 or 2, wherein the component (A) is acombination of a hydrophobic polymer and a hydrophilic polymer.
 4. Acomposition according to any one of claims 1 to 3, wherein the component(A) is a combination of a silicone polymer or a polymer having afluorinated carbon chain and a hydrophilic polymer.
 5. A compositionaccording to claim 4, wherein the silicone polymer is anoxazoline-modified organopolysiloxane having an organopolysiloxanesegment (a) and a poly(N-acylalkyleneimine) segment which is bonded tothe segment (a) at the end or side chain in the molecule thereof via ahetero-atom-containing alkylene group and consists of repeating unitsrepresented by the following formula (1):

(wherein, R¹ represents a hydrogen atom, a C₁₋₂₂ alkyl group, acycloalkyl group, an aralkyl group or an aryl group, and k stands for 2or 3), wherein the weight average molecular weight ranges from 50000 to500000 and a weight ratio of (a) to (b) ranges from 98:2 to 40:60.
 6. Acomposition according to any one of claims 3 to 5, wherein thehydrophilic polymer is polyvinyl alcohol.